Background

Serum preptin levels among subjects with different bone mineral densities (BMD) were measured and investigated to determine the correlation between BMD and bone-metabolic markers.

Methods

Approximately 52 elderly male patients with osteoporosis, 50 elderly men with osteopaenia, and 31 age-matched normal bone mass controls participated in the study. The serum preptin levels and bone metabolic markers were measured by enzyme-linked immunosorbent assay. The relationships between preptin levels, BMD, and metabolic parameters were also assessed.

Results

The serum preptin level was the lowest in the osteoporosis group and positively correlated with BMD. All the bone formation markers in the osteoporosis and osteopaenia groups were significantly reduced compared with those in the normal group. Serum preptin level was positively correlated with all the bone formation markers, whereas no correlation was observed with the bone resorption marker TRACP-5b.

Conclusions

Serum preptin levels are decreased in osteoporosis and osteopaenia patients and positively correlated with BMD. Therefore, preptin is involved in the pathogenesis of osteoporosis, probably through bone formation rather than bone resorption.

Cromolyn sodium (cromolyn) effectively inhibits both antigen- and exercise-induced asthma when used as an aerosol. Intranasal cromolyn is also recommended for preventing and treating allergic rhinitis. By inhibiting the degranulation of sensitized mast cells, cromolyn reduces the release of mediators that trigger inflammation and the allergic response. The precise pharmacologic activity of cromolyn has not been fully elucidated. This study evaluated the effect of cromolyn on isolated rat's trachea. The following assessments of cromolyn were performed: (1) effect on tracheal resting tension, (2) effect on contraction caused by 10−6 M of methacholine as a parasympathetic mimetic, and (3) effect of the drug on electrically induced tracheal contractions. The results indicated cromolyn could inhibit electrical field stimulation-induced spike contraction when the preparation was increased to 10−4M. Adding cromolyn at doses of ≥10−8 M did not elicit a relaxation or contraction response to 10−6 M of methacholine-induced contraction. It alone had a minimal effect on the basal tension of the trachea as the concentration increased. This study indicates cromolyn had no cholinergic or anticholinergic effect and high concentrations of cromolyn might actually inhibit parasympathetic function of the trachea. Inhibiting parasympathetic function of the trachea through stabilizing the presynaptic nerve by cromolyn may be responsible for protecting patients against antigen- and exercise-induced asthma.

In this work we report the characterization of plasmid pCTX-M360, isolated from a Klebsiella pneumoniae strain from China and encoding the CTX-M-3 extended-spectrum β-lactamase. Sequence analysis of pCTX-M360 revealed extensive similarity with pEL60 and pCTX-M3, two other enterobacterial plasmids of the IncL/M incompatibility group. Compared to pEL60, pCTX-M360 contains several insertions but lacks most of a 27-kb insert found in pCTX-M3, suggesting that it could be an evolutionary intermediate between pEL60 and pCTX-M3.

We tested the herbal extract 2,3,5,6-tetramethylpyrazine (TMP) for possible therapeutic efficacy against a glioma cell line and against gliomas transplanted into rat brains. In the cultured glioma cells, 50 μM TMP significantly inhibited glutamate-induced increase in intracellular calcium. Significant cell damage (30%) and proliferation suppression (10%), however, occurred only at higher concentrations (200–400 μM). Glioma- neuronal co-culturing resulted in significant neuronal damage and higher proliferation of the glioma cells (140%) compared with single cultures. Low concentrations of TMP (⩽200 μM) attenuated the neuronal damage, suppressed glioma migration, and decreased glioma proliferation in the neuronal-glioma co-culture. Gliomas transplanted into the frontal cortical area exhibited high proliferation, with untreated rats dying 10–23 days later. TMP treatment inhibited tumor growth and significantly extended survival time. The results indicate that TMP can suppress glioma activity, including growth, and protect neurons against glioma-induced excitotoxicity, suggesting that TMP may have therapeutic potential in the treatment of malignant gliomas.

Background

Intracerebral hemorrhage (ICH) remains a serious clinical problem lacking effective treatment. Urocortin (UCN), a novel anti-inflammatory neuropeptide, protects injured cardiomyocytes and dopaminergic neurons. Our preliminary studies indicate UCN alleviates ICH-induced brain injury when administered intracerebroventricularly (ICV). The present study examines the therapeutic effect of UCN on ICH-induced neurological deficits and neuroinflammation when administered by the more convenient intraperitoneal (i.p.) route.

Methods

ICH was induced in male Sprague-Dawley rats by intrastriatal infusion of bacterial collagenase VII-S or autologous blood. UCN (2.5 or 25 μg/kg) was administered i.p. at 60 minutes post-ICH. Penetration of i.p. administered fluorescently labeled UCN into the striatum was examined by fluorescence microscopy. Neurological deficits were evaluated by modified neurological severity score (mNSS). Brain edema was assessed using the dry/wet method. Blood-brain barrier (BBB) disruption was assessed using the Evans blue assay. Hemorrhagic volume and lesion volume were assessed by Drabkin's method and morphometric assay, respectively. Pro-inflammatory cytokine (TNF-α, IL-1β, and IL-6) expression was evaluated by enzyme-linked immunosorbent assay (ELISA). Microglial activation and neuronal loss were evaluated by immunohistochemistry.

Results

Administration of UCN reduced neurological deficits from 1 to 7 days post-ICH. Surprisingly, although a higher dose (25 μg/kg, i.p.) also reduced the functional deficits associated with ICH, it is significantly less effective than the lower dose (2.5 μg/kg, i.p.). Beneficial results with the low dose of UCN included a reduction in neurological deficits from 1 to 7 days post-ICH, as well as a reduction in brain edema, BBB disruption, lesion volume, microglial activation and neuronal loss 3 days post-ICH, and suppression of TNF-α, IL-1β, and IL-6 production 1, 3 and 7 days post-ICH.

Conclusion

Systemic post-ICH treatment with UCN reduces striatal injury and neurological deficits, likely via suppression of microglial activation and inflammatory cytokine production. The low dose of UCN necessary and the clinically amenable peripheral route make UCN a potential candidate for development into a clinical treatment regimen.